8-60209160-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004056.6(CA8):c.739-241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,014 control chromosomes in the GnomAD database, including 10,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (10784 hom., cov: 32)
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86

Genes affected

CA8 (HGNC:1382): (carbonic anhydrase 8) The protein encoded by this gene was initially named CA-related protein because of sequence similarity to other known carbonic anhydrase genes. However, the gene product lacks carbonic anhydrase activity (i.e., the reversible hydration of carbon dioxide). The gene product continues to carry a carbonic anhydrase designation based on clear sequence identity to other members of the carbonic anhydrase gene family. The absence of CA8 gene transcription in the cerebellum of the lurcher mutant in mice with a neurologic defect suggests an important role for this acatalytic form. Mutations in this gene are associated with cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CMARQ3). Polymorphisms in this gene are associated with osteoporosis, and overexpression of this gene in osteosarcoma cells suggests an oncogenic role. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-60209160-T-C is Benign according to our data. Variant chr8-60209160-T-C is described in ClinVar as [Benign]. Clinvar id is 1220589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA8	NM_004056.6	c.739-241A>G		intron_variant		ENST00000317995.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA8	ENST00000317995.5	c.739-241A>G		intron_variant		1	NM_004056.6	P1
CA8	ENST00000524872.5	n.977-241A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56107 AN: 151896 Hom.: 10771 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.369 AC: 56141 AN: 152014 Hom.: 10784 Cov.: 32 AF XY: 0.367 AC XY: 27304 AN XY: 74308

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.377

Alfa AF: 0.384 Hom.: 1419

Bravo AF: 0.369

Asia WGS AF: 0.287 AC: 1002 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.034
Dann	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35437140; hg19: chr8-61121719;